Field of the Invention
The present invention relates to compositions and methods for reducing the reproductive capacity of mammals. The compositions and methods involve the use and administration of (a) a diterpenoid epoxide comprising a triptolide skeleton and which causes ovarian follicle depletion in female mammals in combination with (b) an organic diepoxide which causes ovarian follicle depletion in female mammals.
Description of the Background
Compositions that reduce the reproductive capacity of mammals, particularly those which induce ovarian follicle depletion, may be desirable for a variety of reasons. Such compositions may be used to induce infertility in pests, such as rodents, to control the population of the pests, and to produce animal models for study. For example, animals, such as rats, with induced follicle depletion can be used to create animal models that can be used to study menopause in and its effects on other animals, such as humans.
Rodent pests are a major cause of damage to the world's agricultural crops and food stores. Rodents eat and contaminate food supplies, carry diseases, damage infrastructure, and can disrupt indigenous wildlife and ecosystems. For decades, rodenticides have been used to try to control rodent populations, yet, to date, rodent populations prove difficult to control and rodent damage is widespread. One reason that rodent populations are difficult to control is that rodents tend to have relatively short gestation periods (e.g., on the order of a few weeks), and thus, unless the entire population is eliminated, the population can restore itself once the rodenticide is exhausted or depleted. In addition, poisons may not specifically target the pests and may affect other animals, including humans. Thus, the use of pesticides may be tempered by other environmental concerns.
The rate of rat reproduction is tied to the quantity of food available and the quality of food sources. Thus, while poisoning reduces the population, it also reduces competition for food, so survivors' reproduction may go unchecked.
A promising alternative to using rodenticides involves using formulations that accelerate ovarian follicle depletion to manage populations of rodent pests via fertility control. The epoxide 4-vinylcyclohexene diepoxide (VCD) has been efficacious to cause non-regenerating primordial follicle depletion in Sprague Dawley rats (Rattus norvegicus) via gavage. However, to be effective for population management, it is desirable to target multiple, e.g., all, ovarian follicles for depletion, so to have an immediate impact on fertility and pup production. Accordingly, improved compositions that induce ovarian follicle depletion at multiple stages and methods of using the composition are desired.